PXD063604-1
PXD063604 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Illuminating oncogenic KRAS signaling by multi-dimensional proteomics |
| Description | Mutated KRAS is among the most frequent activating genetic alterations in cancer and drug discovery efforts have led to inhibitors that block its activity. To better understand oncogenic KRAS signaling and the cytostatic effects of drugs that target this system, we performed comprehensive dose-dependent proteome-wide target deconvolution, pathway engagement and protein expression characterization of KRAS, MEK, ERK, SHP2 and SOS1 inhibitors in pancreatic (KRAS G12C, G12D) and lung cancer (KRAS G12C) cells. Analysis of the resulting 715,239 dose-response curves available online established that KRAS inhibitors are very selective. In addition, cross-cell comparisons of phosphoproteomes revealed a core KRAS signaling signature as well as cell line-specific signaling networks. In all cell lines phosphoproteomes were dominated by different degrees of autonomous oncogenic KRAS activity. Comparing the phosphoproteomes of short and long drug exposures allowed the distinction of early KRAS-MEK-ERK signaling from the consequences of cells exiting the cell cycle. This transition to a quiescent state occurred in the absence of substantial proteome re-modelling but broad changes of protein phosphorylation and ubiquitylation. The transition also included the participation of ubiquitylation -mediated inhibition of E1 ubiquitin activating and E2 ubiquitin conjugating enzymes. The collective data provides new views on KRAS signaling, highlights the molecular complexity of this system in cancer, places a large number of new proteins into this functional context and offer a general mechanism of how cancer cells escape death from signaling inhibitors. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-06-13 |
| AnnouncementXML | Submission_2025-06-13_09:42:59.571.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Nicole Kabella |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Phospho; GG |
| Instrument | Orbitrap Fusion Lumos; Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-05-05 07:06:32 | ID requested | |
| ⏵ 1 | 2025-06-13 09:43:00 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: KRAS, Phosphoprotemics, Ubiquitinome, Cancer, PTM, DatasetType:Proteomics |
Contact List
| Bernhard Kuster | |
|---|---|
| contact affiliation | Chair of Proteomics and Bioanalytics, Technical University of Munich |
| contact email | kuster@tum.de |
| lab head | |
| Nicole Kabella | |
| contact affiliation | Technical university of Munich |
| contact email | nicole.kabella@tum.de |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v09/MSV000097797/ |
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